Mgs1 protein supports genome stability via recognition of G-quadruplex DNA structures

Zacheja, Theresa and Tóth, Ágnes and Harami, Gábor and Yang, Qianlu and Schwindt, Eike and Kovács, Mihály and Burkovics, Péter (2020) Mgs1 protein supports genome stability via recognition of G-quadruplex DNA structures. FASEB JOURNAL, 34 (9). pp. 12646-12662. ISSN 0892-6638

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Abstract

The integrity of the genetic material is crucial for every organism. One intrinsic attack to genome stability is stalling of the replication fork which can result in DNA breakage. Several factors, such as DNA lesions or the formation of stable secondary structures (eg, G-quadruplexes) can lead to replication fork stalling. G-quadruplexes (G4s) are well-characterized stable secondary DNA structures that can form within specific single-stranded DNA sequence motifs and have been shown to block/pause the replication machinery. In most genomes several helicases have been described to regulate G4 unfolding to preserve genome integrity, however, different experiments raise the hypothesis that processing of G4s during DNA replication is more complex and requires additional, so far unknown, proteins. Here, we show that the Saccharomyces cerevisiae Mgs1 protein robustly binds to G4 structures in vitro and preferentially acts at regions with a strong potential to form G4 structures in vivo. Our results suggest that Mgs1 binds to G4-forming sites and has a role in the maintenance of genome integrity.

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